DESCRIPTION (applicant?s abstract): The hormonal control of apoptosis (cell death) sculpts many morphological sex differences in the nervous system. Very little, however, is known about how hormones affect apoptosis. I want to explore the intracellular mechanisms of cell death that may be controlled by gonadal hormones during sexual differentiation of the nervous system. The Bcl-2 family of proteins has been shown to regulate apoptosis in many different cell types, including neurons. This proposal will examine the role of Bcl-2 family members during sexual differentiation of a relatively simple model system: the spinal nucleus of the bulbocavernosus (SNB) and its target perineal muscles. The SNB is a sexually-dimorphic cluster of motoneurons in the lumbar spinal cord. Adult males have 3-4 times more SNB motoneurons than females, a difference due to androgen-regulated cell death occurring perinatally. Using the SNB as the primary model system, I will evaluate the link between testosterone and molecules regulating neuronal apoptosis. Evidence gleaned from this model system may be applicable to the more complex arena of sexual differentiation in the brain. This idea will be explored in the final study of this proposal.